Taste is importantly involved in food intake and in the etiology and treatment of nutrition-related disorders. Therefore, knowledge of taste function is essential for health care and maintenance. This proposal is to initiate research to study sweet taste by a genetic approach in humans. The immediate goal is to describe the basic genetics of human sweet taste. The long-term goal is to use functional and genetic information from humans and Drosophila to identify transduction molecules and their physiological roles in sweet taste. Human psychophysical functions for sweetness are similar for sucrose and fructose, but different for glucose, and suggest different mechanisms for the monosaccharides. The existence of different mechanisms suggested that individuals could be found who are defective in tasting one monosaccharide or the other. The proposed research is to describe the genetic component of the different mechanisms in humans by testing taste sensitivities across generations and by examining the sensitivities of persons with and without diabetes mellitus (DM), a genetic disorder which may involve decreased sensitivity for glucose taste. The work will progress in three phases: 1) studies of responses of nondiabetics and diabetics to the three sugars, 2) identification of nontasters (NTs) for fructose or glucose, and 3) testing members of NTs' families in order to construct pedigrees for the heritability of the NT traits. This research will launch a program in which quantitative techniques for analysis of polygenic, multifactorial disorders, together with emerging technologies for large scale molecular analyses in human genetics provide a powerful approach for future research.